The Harvey sarcoma virus was derived by recombination between a murine leukemia virus and rat cellular sequences. Two rat genes (designated cRAS-l and cRAS-2) which are homologous to the Harvey virus transforming gene (RAS) have been identified. However, only the cRAS-l gene can be activated and will transform NIH 3T3 cells in a DNA transfection assay, whereas the cRAS-2 gene does not transform NIH 3T3 cells. Although both cRAS-1 and the Harvey RAS gene encode similar p21 proteins that induce transformation, these proteins also exhibit differences. For example, a significant proportion of the Harvey p21 is phosphorylated while little if any of the cRAS-l p21 is phosphorylated. In order to understand he differences between the cRAS-l and Harvey RAS genes and to determine the nature of the defect in cRAS-2,nucleotide sequencing of the cRAS-l and cRAS-2 genes was initiated. The cRAS-1 sequence determined thus far shows extensive homology to the known sequence of the Harvey RAS gene. In addition, the metabolism of the cRAS-l and Harvey p21 proteins was analyzed.